Development of ITI-333, a μ-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders
开发 ITI-333,一种 μ-阿片受体部分激动剂和 5HT2A 和 D1 受体拮抗剂,用于治疗阿片类药物使用障碍
基本信息
- 批准号:9841388
- 负责人:
- 金额:$ 291.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-01-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdverse eventAffinityAgonistAnimalsAnxietyBindingBiological ProductsBiotechnologyBrainCentral Nervous System DiseasesClinicalClinical PathsClinical ResearchClinical TrialsCollaborationsConduct Clinical TrialsDataDevelopmentDevelopment PlansDopamineDopamine D1 ReceptorDoseDose-LimitingDouble-Blind MethodDrug KineticsExhibitsFentanylFormulationFundingFutureGoalsGrantHTR2A geneHeroinHeroin UsersHumanImageIndividualInpatientsMaintenanceMaximum Tolerated DoseModelingMorphineNational Institute of Drug AbuseOpiate AddictionOpioidOpioid AntagonistOpioid ReceptorOpioid agonistOutcomeOverdoseParentsPathway interactionsPatientsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhasePlacebosPlasmaPositronPrecipitationPrincipal InvestigatorRegimenRelapseResearch PersonnelRouteSafetySerotoninSerotonin Receptor 5-HT2ASignal TransductionTherapeuticTherapeutic IndexTherapeutic UsesToxicologyWithdrawalassociated symptombasecarfentanilclinical developmentdepressive symptomsdesigneffective therapyfirst-in-humanhealthy volunteerillicit opioidin vivoinnovationmolecular drug targetmu opioid receptorsnovelopioid abuseopioid useopioid use disorderopioid useropioid withdrawalphase 2 studyprescription opioidpreventprogramsradioligandreceptorresearch clinical testingsmall moleculesymptom treatmentvolunteer
项目摘要
RFA-DA-19-002 Principal Investigator/PD: Vanover, Kimberly E.
Project Summary/Abstract
Intra-Cellular Therapies Inc (ITI), a clinical-stage biopharmaceutical company, is developing ITI-333, a novel
compound with high affinity activity at mu opiate (MOP), 5-HT2A, and D1 receptors. The nonclinical profile of
ITI-333 suggests a promising medication, lacking abuse liability, with partial agonist activity at MOP
receptors useful for treatment of opiate withdrawal in individuals with Opioid Use Disorders (OUD). ITI is
currently completing IND-enabling nonclinical safety, toxicology, pharmacokinetic and manufacturing
activities, with the goal of launching Phase 1 human clinical evaluation of ITI-333 in healthy volunteers in Q1
2019. ITI seeks to partner with NIDA in the development of this compound for a novel and safe therapeutic
for use in treating OUD, requesting support of clinical development of ITI-333, while committing significant
internal funds to a parallel program of non-clinical development and CMC activities in support of the clinical
plan. To this end, we submit this application, “Development of ITI-333, a µ-opioid Receptor Partial
Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders” to NIDA
RFA-DA-19-002, Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose
(UG3/UH3). Here, we propose a 2-year UG3 program, including a First-in-Man, single ascending dose
(SAD) study (ITI-333-001) to assess the safety, tolerability and pharmacokinetics of ITI-333 in healthy
volunteers. The safety, tolerability, and pharmacokinetics of multiple, ascending doses (MAD) of ITI-333 will
then be evaluated in a single-center in-patient study (ITI-333-002) with the goal of determining a maximally-
tolerated dose (MTD). Both studies will be conducted in collaboration with Clinilabs, a NYC-based CRO. In
parallel with the MAD study, we will characterize the in vivo receptor pharmacology of ITI-333 at MOP, 5-
HT2A, and D1 receptors in human brain using PET imaging (with Dr. Dean Wong, JHU, ITI-333-003), thereby
leveraging our SAD data to clinically validate the mechanism of action of ITI-333 and to inform Phase 2
dose selection. These data will enable us to launch a 3-year UH3 program exploring the human abuse
liability (HAL) and functional pharmacology of ITI-333 in collaboration with Dr. Sandra Comer (CUMC), a
clinical expert in opioid use and abuse. The HAL study (Phase 2a, ITI-333-004) will characterize the opioid
receptor antagonist/partial agonist profile of ITI-333 in humans to explore potential abuse liability in humans.
Additional Phase 2 studies will evaluate the in vivo functional pharmacology of ITI-333 in a model of
withdrawal precipitation in non-treatment seeking heroin users (ITI-333-005) and in a model of mu-opioid
receptor blockade in treatment-seeking heroin users (ITI-333-006). Together, we believe this clinical
development plan with inform further development of ITI-333 and the selection of a cogent Phase 3 clinical
path toward FDA approval as a medication for the treatment of OUD.
RFA-DA-19-002主要研究者/PD:Vanover、Kimberly E.
项目总结/摘要
细胞内治疗公司(ITI),一家临床阶段的生物制药公司,正在开发ITI-333,一种新的
对μ阿片(MOP)、5-HT 2A和D1受体具有高亲和力活性的化合物。的非临床特征
ITI-333表明是一种有前途的药物,无滥用倾向,在MOP下具有部分激动剂活性
用于治疗阿片类药物使用障碍(OUD)个体的阿片类药物戒断的受体。ITI正在
目前正在完成IND使能性非临床安全性、毒理学、药代动力学和生产
活动,目标是在第一季度在健康志愿者中启动ITI-333的1期人体临床评价
2019. ITI寻求与NIDA合作开发这种化合物,用于新型安全的治疗
用于治疗OUD,请求支持ITI-333的临床开发,同时承诺
内部资金用于非临床开发和CMC活动的平行计划,以支持临床
计划为此,我们提交了这份申请,“开发ITI-333,一种μ-阿片受体部分
激动剂和5 HT 2A和D1受体拮抗剂,用于治疗阿片类药物使用障碍”至NIDA
RFA-DA-19-002,预防和治疗阿片类药物使用障碍和过量的药物开发
(UG3/UH3)。在这里,我们提出了一个为期2年的UG 3计划,包括首次在人,单次剂量递增
(SAD)评估ITI-333在健康受试者中的安全性、耐受性和药代动力学的研究(ITI-333-001)
志愿者多次递增剂量(MAD)ITI-333的安全性、耐受性和药代动力学将
然后在单中心住院患者研究(ITI-333-002)中进行评价,目的是确定最大-
耐受剂量(MTD)。这两项研究都将与纽约市的CRO Clinilabs合作进行。在
与MAD研究平行,我们将描述ITI-333在MOP,5-
HT 2A和D1受体在人脑中使用PET成像(与Dean Wong博士,JHU,ITI-333-003),从而
利用我们的SAD数据在临床上验证ITI-333的作用机制,并为第2阶段提供信息
剂量选择这些数据将使我们能够启动一个为期3年的UH 3项目,探索人类虐待
责任(HAL)和ITI-333的功能药理学与Sandra Comer博士(CNODC)合作,
阿片类药物使用和滥用方面的临床专家。HAL研究(2a期,ITI-333-004)将描述阿片类药物
受体拮抗剂/部分激动剂特性,以探索人类中的潜在滥用倾向。
另外的2期研究将评估ITI-333的体内功能药理学,
非寻求治疗的海洛因使用者(ITI-333-005)和μ阿片类药物模型中的戒断沉淀
寻求治疗的海洛因使用者中的受体阻滞(ITI-333-006)。我们相信,这种临床
开发计划,包括ITI-333的进一步开发和选择令人信服的3期临床试验
通往FDA批准作为治疗OUD的药物的道路。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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